Low-voltage Electrocorticogram Research Articles

Central cholinergic mechanisms mediate swallowing, renal excretion, and c-fos expression in the ovine fetus near term

Fetal swallowing and renal metabolism contribute importantly to amniotic and body fluid homeostasis. To determine central cholinergic modulation of swallowing activity and renal excretion associated with neural activity, we examined the effects of intracerebroventricular injection of carbachol, a cholinergic agonist, in ovine fetuses at 0.9 gestation. Fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram electrodes, as well as lateral ventricle and vascular catheters. Electrodes were also implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, and urine output were monitored during basal period and the experimental period following intracerebroventricular injection of 0.9% NaCl as the control (n = 5) or carbachol (3 microg/kg, n = 5). Central carbachol did not significantly change fetal low voltage (LV) and high voltage (HV) ECoG temporal distributions. However, swallowing activity during LV ECoG was elevated significantly after intracerebroventricular carbachol. Associated with the swallowing activation, c-fos immunoreactivity in the putative dipsogenic center, subfornical organ, was enhanced significantly. The fetal urine flow rate and renal Na+, K+, and Cl(-) excretion were markedly increased following intracerebroventricular carbachol and sustained at the high level for at least 2 h. The results indicate that the central cholinergic mechanism is established and functional in regulation of fetal behavior and renal excretion at least at 0.9 gestation, which plays an important role in maintenance of fetal body fluid homeostasis.

Central neuropeptide Y stimulates ingestive behavior and increases urine output in the ovine fetus.

We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 +/- 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY significantly increased swallowing activity during low-voltage ECoG from basal activity (1.26 +/- 0.15 swallows/min) at 4 h (1.93 +/- 0.37 swallows/min), 6 h (1.69 +/- 0.27 swallows/min), and 8 h (2.38 +/- 0.31 swallows/min). NPY significantly increased fetal urine flow (basal: 0.13 +/- 0.02; 4 h: 0.21 +/- 0.04; 6 h: 0. 19 +/- 0.03 ml.kg(-1).min(-1)). These results demonstrate that central NPY stimulates fetal swallowing activity and increases urine output, which may contribute to the in utero development of ingestive behavior.

Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus.

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 +/- 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) and monitored for 2 h. NO precursor L-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test (P < 0.05). Suppression of a central NO with central L-NAME significantly reduced mean (+/-SE) spontaneous fetal swallowing (1.2 +/- 0.1-0.6 +/- 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by L-arginine significantly increased fetal swallowing to pre-L-NAME levels (1.2 +/- 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.

Electrocortical activity in fetal sheep in the last seven days of gestation.

1. Electrocorticogram (ECoG) and myometrial electromyogram (EMG) were recorded continuously in chronically instrumented late gestation sheep fetuses (n = 9) to analyse: (1) 24 h ECoG patterns, (2) relationships between ECoG and myometrial contractility, and (3) 24 h ECoG patterns at the spontaneous onset of labour. 2. Spontaneous onset of labour was determined from the myometrial EMG. ECoG signals were purified by a denoising procedure of wavelet decomposition. High-voltage slow ECoG activity (HV) and low-voltage fast ECoG activity (LV) were determined mathematically, and HV-LV cycle periodicity was calculated by periodogram analysis. 3. Twenty-four hour rhythms were present in fetal ECoG HV-LV cycles in the 3-5 days prior to spontaneous onset of labour (P < 0.01). Cycle frequency was lower at 08.00-12.00 h and higher at 16.00-20.00 h (lights on at 07.00 h, lights off at 21.00 h). LV duration was longer at 20.00-24.00 h, and HV was shorter at 16.00-20.00 h. No relationship was found between ECoG cycles and myometrial contracture cycles. Twenty-four hour ECoG rhythms disappeared 1 day before the spontaneous onset of labour. 4. ECoG patterns changed 7 to 4 h prior to spontaneous onset of labour, percentage of time spent and duration of HV ECoG increased, and percentage of time spent in LV decreased significantly. ECoG HV-LV cyclicity was reduced 4-5 h prior to spontaneous onset of labour, indicating that the altered fetal hormonal and blood gas environment around the spontaneous onset of labour alter fetal neural function.

Carotid blood flow changes with behavioral states in the late gestation llama fetus in utero

This study tested the hypothesis that in the llama fetus changes in cerebral blood flow are closely associated with changes in cerebral oxidative metabolism such as occur during transitions between electrocortical states. For the first time reported in any species, instantaneous changes in common carotid blood flow, employed as a continuous index of cerebrovascular perfusion, were related to instantaneous changes in electrocortical activity. Three late gestation fetal llamas were surgically prepared under general anesthesia with vascular catheters, a tracheal and amniotic catheter, and with electrodes implanted to monitor the fetal electrocorticogram (ECoG). In addition, Transonic flow probes were placed around a common carotid artery and a femoral artery. At least 4 days after surgery fetal arterial blood, amniotic and tracheal pressures, carotid and femoral blood flows and the fetal ECoG were recorded continuously. Our results suggest a close association between increases in common carotid blood flow and low voltage ECoG in the llama fetus. Close coupling between instantaneous changes in carotid blood flow and electrocortical states together with the lack of an increase in brain blood flow without increased cerebral oxygen extraction during hypoxemia in the llama fetus supports a fall in cerebral oxidative metabolism in this species during hypoxemic episodes.

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs

OBJECTIVE: Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. STUDY DESIGN: Eleven trials of arginine vasopressin infusion (40 to 160 mIU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 μg). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. RESULTS: Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. CONCLUSION: These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns. (AM J OBSTET GYNECOL 1994;170:1421-4.)

Experimentally induced intermittent sinusoidal heart rate pattern and sleep cycle in fetal lambs

<b>OBJECTIVE:</b> Intermittent sinusoidal heart rate pattern, an early indicator of fetal anemia, has been speculated to have a positive correlation with fetal sleep cycles. To test this hypothesis, intermittent sinusoidal heart rate patterns were produced experimentally with arginine vasopressin in six methylatropinized fetal lambs that were demonstrating clear rapid-eye-movement and non-rapid-eye-movement sleep cycling. <b>STUDY DESIGN:</b> Eleven trials of arginine vasopressin infusion (40 to 160 mlU per body per minute) were performed on each of six chronically instrumented fetal lambs subsequent to parasympathetic blocking doses of methylatropine (300 to 400 μg). An intermittent sinusoidal heart rate pattern was observed in relation to fetal sleep cycles. <b>RESULTS:</b> Alteration between rapid-eye-movement and non-rapid-eye-movement sleep was observed in methylatropinized fetuses. In the six fetuses that showed intermittent sinusoidal heart rate patterns subsequent to arginine vasopressin infusion, the fetal heart rate tracing and fetal electrocorticogram demonstrated alternate sinusoidal pattern and reactive heart rate patterns during high- and low-voltage electrocorticogram activity, respectively. <b>CONCLUSION:</b> These findings support the hypothesis that fetal sleep cycling has a positive correlation with the periodic appearance of intermittent sinusoidal heart rate patterns.

Variable fetal heart rate decelerations and electrocortical activities

OBJECTIVE: The purpose of this study was to examine the influence of fetal behavioral states on baroreflex-mediated, variable fetal heart rate decelerations caused by umbilical cord occlusion. STUDY DESIGN: Five chronically instrumented fetal lambs were subjected to intermittent partial umbilical cord occlusion for 1 minute every 3 minutes, lasting 2 hours. Fetal behavioral states determined by electrocorticogram and heart rates by electrocardiogram were monitored continuously during these experiments. RESULTS: The fetuses exhibited an alteration between low- and high-voltage electrocorticogram states. Both the depth and width of the variable fetal heart rate decelerations were greater during high-voltage than during low-voltage electrocorticogram. CONCLUSION: Amplitude and duration of variable fetal heart rate decelerations are affected by fetal behavioral states. (AM J OBSTET GYNECOL 1994;170:689-92.)

Ovine fetal swallowing and behavioral state responses to sublingual water.

Ovine fetal swallowing primarily occurs in bouts of activity associated with low voltage electrocorticogram activity and breathing movements. Despite similar rates of electromyographic swallowing activity, there are significant differences in the net esophageal fluid flow among fetuses. To determine if variations in the volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary secretions) affect fetal swallowing, we studied the effects of sublingual distilled water infusions on ovine fetal swallowing rates and esophageal flow. Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular and electromyograph electrodes, an esophageal flow probe and a sublingual infusion catheter. Following a 2-hour control period, consecutive sublingual infusions of room temperature distilled water (10 and 20 ml/kg/h) were administered for 2 h each. In response to sublingual infusions, fetal plasma sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/- 0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg) decreased significantly. Swallowing activity and esophageal flow did not change significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during the sublingual infusions. However, fetal low-voltage electrocortical activity increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%). Sublingual distilled water infusion decreases fetal plasma osmolality and alters fetal behavioral state without affecting swallowing frequency or esophageal flow.

Cerebral oxidative metabolism in lambs during perinatal period: relationship to electrocortical state.

Cerebral oxidative metabolism and regional blood flow were studied, with changes in behavioral state over the immediate perinatal period, to determine the change in cerebral metabolism at birth and the relationship to behavioral activity. Nine unanesthetized fetal sheep (139-142 days gestation) were each studied during a period of high-voltage and low-voltage electrocorticogram (ECOG) activity and then again after cesarean delivery at 2 h of age while awake and at 24 h of age while awake and during a period of high-voltage ECOG sleep. Preductal arterial and sagittal vein blood samples were analyzed for O2 content, blood gases, and pH. Blood flow was measured with a radioactive microsphere technique. Cerebral oxidative metabolism showed no significant perinatal change, although a coupling to behavioral state was evident with significant increases during both the perinatal low-voltage ECOG state and the awake state at 24 h. Blood flow to the brain showed a significant perinatal decrease after birth and state-related increases during both the prenatal low-voltage ECOG state and the awake state at 24 h consistent with the tight coupling of flow and/or O2 delivery to metabolic needs reported for normal brain tissue. The cerebral metabolic rate of the prenatal low-voltage ECOG state suggested a level of functional excitation comparable with that of the awake state after birth, supporting the importance of the rapid-eye-movement (REM) state mechanism as a source of endogenous stimulation during the perinatal period of brain growth and development.

INGESTION IN FETAL SHEEP AND ITS RELATION TO SLEEP STATES AND BREATHING MOVEMENTS

Swallowing was recorded electromyographically in unanaesthetized fetal sheep in utero during the last third of gestation. In control fetuses bouts of swallowing were, on average, 2.0 min in duration and occurred at intervals of 2.31 h. Swallowing bouts were associated with a low-voltage electrocorticogram, eye movements and, in 82% of instances, with phasic activity in the dorsal neck muscles. These data indicate that fetuses are not in quiet (non-rapid eye movement; n.r.e.m.) sleep when swallowing and also suggest that they are not in r.e.m. sleep as conventionally defined; we consider that fetuses may be in a state of heightened activity resembling wakefulness. Swallowing bouts were always accompanied by fetal breathing movements. When a swallow coincided with an inspiratory effort the diaphragm was briefly inhibited. Evidence was obtained that bouts of fetal ingestive activity were not dependent upon outpourings of fluid from the lungs and were not significantly influenced by volume information from the gastric compartments.

285 DEVELOPMENT OF THE MONOSYNAPTIC AND POLYSYNAPTIC REFLEXES IN THE CHRONIC FETAL SHEEP PREPARATION

We examined the relationship between segmental spinal reflexes and electrocortical activity in fetal lambs from 105-137 days gestational age. Five fetal sheep were studied on 48 occasions. Of these, 4 were older (>120 days) and one was young (105 days onwards). Single shock stimulation (1 to 4mA; 0.1 msec duration; 0.3-0.03 Hz) was used. The mono- and polysynaptic reflexes were elicited by stimulating the sciatic nerve and recording from the peroneal or tibial nerve or vice-versa. The average latency was 3.9 msec for the monosynaptic reflex, and 22 msec for the polysynaptic reflex. In fetuses >120 days gestation both reflexes were reduced or absent in low voltage as compared to high voltage electrocortical activity. In the young fetus (105-115 days) with an undifferentiated electrocorticogram the reflexes were larger during breathing, i.e. in circumstances which correspond to low voltage electrocortical activity later in fetal life. During brief episodes of eye and breathing movements at the transition between high and low voltage electrocortical activity the reflexes were enhanced. It is tempting to speculate that the enhancement of the reflexes during increased eye and breathing movements in low voltage electrocorticogram may indicate wakefulness in utero.

Respiratory function of the larynx in developing sheep and the influence of sleep state

The activities of laryngeal abductor and adductor muscles were recorded in conjunction with other respiratory muscles in unanaesthetized chronically monitored foetal, newborn and adult sheep. In foetuses, rhythmical breathing movements occurred in the presence of rapid eye movements and a low voltage electrocorticogram (REM state) and were accompanied by phasic laryngeal abduction; adductor muscles and intercostals were largely inactive. During the foetal non-REM state laryngeal adductor muscles were tonically active at a low level, but the glottis remained open. Deep inspiratory efforts which occurred at low frequency in this behavioural state were not accompanied by abductor activity and resembled inspiratory efforts associated with regurgitation in ruminants. After birth, expiratory adductive activity of the larynx was also maximal during non-REM sleep and negligible during REM sleep. Active laryngeal adduction was accompanied by delayed expiratory airflow, prolonged T e and reduced respiratory frequency. Adduction of the larynx is dependent on behavioural state and appears to be the principal means of regulating T e in sheep, particularly during early post-natal development.

Ocular phenomena in the two stages of sleep in the cat

The pupil is wider and the nictitating membrane is more retracted in the stage of sleep characterized by a low voltage electrocorticogram than in sleep with slow waves and spindles. The infrapalpebral events suggest an increased sympathetic activity, probably humoral in nature, which may help account for some of the variations in autonomic neuroeffector systems and the persistent electrocortical desynchronization typical of this stage of sleep.